Inhibiting effects of cidofovir (HPMPC) on the growth of the human cervical carcinoma (SiHa) xenografts in athymic nude mice

At present more than 70 human papillomaviruses (HPV) genotypes have been de scribed and each shows a predilection for a cutaneous or mucosal surface. T here is a strong association between infection with specific genital viruse s (i.e., types 16 and 18) and the development of cervical cancer. Thus, int ervention with the natural history of HPV infection in the genital tract ma y form the basis for an effective anticancer strategy. We have shown that t reatment of cell lines derived from human cervical carcinomas [i.e., SiHa a nd CaSki (HPV-16-positive)] and HeLa (HPV-18-positive)] with HPMPC (cidofov ir) results in a concentration- and time-dependent inhibition of cell proli feration. We report here the effects of HPMPC on the growth of cervical car cinoma (SiHa) xenografts in athymic nude mice. Athymic mice between the age of 6 and 8 weeks were injected SC with 5 to 10 x 10(6) cells. Once tumors were established, the mice were injected with PBS (placebo), HPMPC, or cyta rabine (AraC) at the tumor site. Animals that were injected intratumorally with HPMPC at a dose of 5 mg/ml (0.25 mg/injection) or 10 mg/ml (0.5 mg/inj ection) three or five times per week, once daily, during 4 weeks showed a s tatistically significant reduction in tumor size compared to the placebo gr oup or AraC group. However, when HMPC was administered topically las a crea m) or systemically (intraperitoneally), no reduction of tumor growth was ob served at nontoxic concentrations, suggesting that a high local concentrati on of HPMPC is required to achieve a significant decrease of tumor growth.